Investigations of the major histocompatibility complex of the rabbit (RLA) have provided further evidence concerning the similarities and differences between RLA and the well characterized MHC regions of human and mouse. A gene encoding the DO beta chain was cloned and its expression shown to be confined to mature B cells and to thymus. The gene was studied in 8 different haplotypes and coding regions conserved in each, polymorphism was however detected by use of restriction enzymes indicating that flanking sequences not highly conserved. The gene encoding the alpha chain partner of DOB is being sought using probes for the human counterpart. The rabbit should provide an excellent model system in which to study the function of this highly conserved class II molecule. Efforts to construct a complete physical map of the rabbit MHC have progressed. A 380 kb stretch containing class III genes, including those for complement components and for heat shock protein, has been mapped. No class I or class II genes have been linked to this class III cluster by pulsed field electrophoresis, although breeding studies reveal linkage of class III to class I and II genes. A probe for the TNFa gene, which lies between class I and class III in human and mouse, has been prepared and will be used in an attempt to order the various MHC regions in the rabbit.